The Impact of Ageing on Skeletal Muscle: Roles of Mitochondrial Dysregulation, Systemic Communication, and Exercise

Ageing is a major risk factor for degenerative diseases, including sarcopenia, which is characterized by a progressive loss of skeletal muscle mass and function, frailty, and is associated with increased mortality. Skeletal muscle regeneration relies on muscle stem cells and efficient communication with cellular microenvironment. With ageing, skeletal muscle regenerative capacity declines, and sarcopenia results from complex, multitissue dysregulation involving mitochondrial dysfunction, immune ageing, chronic inflammation, senescence, extracellular matrix modification, disruption of neuromuscular junctions and muscle-specific vulnerability. This review summarizes current knowledge contributing to sarcopenia and inefficient muscle repair during ageing from cell-autonomous metabolic dysregulation to age-associated changes in the local and systemic cellular environment. We also explore recent insights into important role of exercise on muscle tissue health. Overall, emerging technologies, including human muscle atlases and spatial transcriptomics, together with exercise-based interventions, will help to identify of novel biomarkers and therapeutic targets to better prevent and treat sarcopenia.